June 2022: Guidance on Complex Clinical Trials

European Medicines Agency (EMA) updated the page Clinical Trials in Human Medicines on June 03, 2022, by providing information on complex clinical trials and adding the below document:

Complex clinical trials – questions and answers: It provides answers to the questions related to planning, designing, and conducting complex clinical trials and master protocols. It also guides on transparency requirements and reporting clinical trial information to regulatory authorities.

It explains in detail the definition of ‘end of trial’, requirements of end of trial date, end of sub-protocol date, and/or premature end of sub-protocol date for submitting the complex clinical trial at all three levels (member state, European Union [EU] level, and global level) in Clinical Trials Information System (CTIS). It mentions that a protocol should include a plan for smooth communication between the relevant stakeholders (e.g. investigators, CROs, regulatory authorities, ethics committees, trial participants, and sponsors when there are more than one) to maintain the integrity of the trial. It also mentions that if there are any changes in the communication plan, a substantial protocol should be created.

All documents should be identified either with a common identifier or a specific identifier. It enlists the documents required to gain access to personal data or commercially confidential information, if more than one sponsor is involved in the trial, and while submitting the master and sub-protocols. There should be a section of publication policy in either of the protocols (master or sub-protocol) at the time when data needs to be published that includes the following:

  1. Sponsor’s commitment to notify the actual study dates along with the dates of sub-protocols to fulfill EU CTR transparency requirements
  2. Sponsor’s commitment to submit the summary results within a year following the end of the sub-protocol date, or a reason for delay if not submitted within the timeline.
  3. A valid justification to defer the publication of sub-protocol results

It also mentions if the complex trial has several study phases, the highest phase should be applied. If there are any restrictive changes in the publication policy, a substantial modification will be triggered.